The skin consists of three main layers: stratum corneum, epidermis and dermis. The skin is a primary defense barrier of the human body, which functions to protect various organs in the body from changes in temperature and humidity, and external environmental irritants such as UV and pollutants, this barrier function of skin depends on the physical and chemical properties of the stratum corneum present in the skin's outermost layer. The stratum corneum consists of keratinocytes, containing a keratin protein as a main component, and a lipid layer between the cells. It is known that, in the absorption of substances into the skin, the substances are actually very difficult through the keratinocytes, and are generally passed through the lipid layer between the keratinocytes. Thus, the skin absorption of fat-soluble substances such as tocopherol is relatively smooth, whereas substances difficult to distribute in the lipid layer, and high-molecular weight active ingredients, are not easy to absorb into the skin.
Till now, in order to increase the skin absorption of active ingredients having low skin absorption, many particle delivery systems, including nanoparticles employing high-molecular-weight copolymers, liposomes, deformable vesicles and nanoemulsions, have been studied. In the case of nanoparticles that use polyethylene/polycaprolactone copolymers containing Minoxidil, when they were applied to the skin of hairy guinea pigs and measure for the skin absorption thereof, it could be seen that the skin absorption thereof was higher than those of general liposome or 30% ethanol, containing the same amount of Minoxidil (J. Shim et al., J. Control. Release (2004) 97, 477).
Also, Korean Patent Laid-Open Publication No. 2005-0099213 discloses that each of a liposome, containing Rheum undulatum as a skin whitening active ingredient, and a solvent mixture (alcohol: butyleneglycol=7:3) containing the same amount of Rheum undulatum, was applied to the Franz permeation cell, and the skin absorption thereof with time was measured and, as a result, the skin absorption in the use of the liposome was 9-fold higher than in the use of the solvent.
Transfersome, a typical deformable vesicle, consists of phospholipid and a single-chain surfactant. In this case, it is thought that the single-chain surfactant increases the deformation of a lipid double layer by unstabilizing the lipid double layer and lowering the interfacial tension thereof. It was found that, when diclofenac as an arthritis therapeutic agent encapsulated in commercial hydrogel and transfersome was applied on the animal skin, the use of the transfersome had an improved ability to deliver the drug into the skin.
Thus, the retention time of the drug in intestinal organs was increased, so that the amount of the drug, required to obtain therapeutic effects, was reduced to 1/10 compared to the drug amount required in hydrogel (Cevc G, Blume G, Biochim. Biophys. Acta. (2001) 1514, 191).
Korean Patent Laid-Open Publication No. 2003-0069246 discloses a method for preparing a nanoemulsion having increased skin absorbability, which is prepared using a lecithin mixture of a controlled mixing ratio of saturated lecithin and unsaturated lecithin as a surfactant and contains one or more oils or physiologically active ingredients in the inner phase of nanoparticles and water in the outer phase.
These prior methods increased the skin absorption of active ingredients, but are not yet satisfactory or studied so as to be applicable to cosmetics.
Recently, studies have been actively conducted to stabilize oil-soluble active ingredients, which are widely used in cosmetics due to excellent effects such as skin wrinkle improvement and skin-moisturizing enhancement, but have problems in that they are easily discolored and degraded due to contact with external factors such as air or water and show a decrease in titer, leading to a reduction in effect. Among such active ingredients, retinol receives great attention due to excellent effects such as wrinkle-preventing effects, but is one of the most unstable components, which are easily broken by light, heat, air and water, and thus the use thereof is extremely limited.
Methods for stabilizing retinol in formulations to overcome such limitations will now be described in detail. EP Publication No. 440398 and PCT International Patent Publication No. 93/00085 disclose techniques for stabilizing retinol in the form of an oil-in-water emulsion by adding an antioxidant and a chelating agent. Also, U.S. Pat. No. 5,851,538 discloses porous microspheres for improving the stability of retinol and reducing skin irritation. In addition, U.S. Pat. No. 6,183,774 discloses a method for stabilizing retinol using cationic liposome, and U.S. Pat. No. 5,985,296 discloses a method for stabilizing retinol using cyclodextrin. Also, U.S. Pat. No. 6,565,886 discloses a method for stabilizing retinol using alkylene adipate nanocapsules. Such prior methods improved the stability of retinol, but are not yet satisfactory, and there is an urgent need to invent a system which can be widely used to stabilize oil-soluble active ingredients other than retinol.
Generally, in an attempt to increase the skin absorption of oil-soluble active ingredients, methods for reducing the size of capsules containing oil-soluble active ingredients are being widely studied. Thus, initial studies on microparticles have progressed to studies on nanoparticles. However, when polymer capsules having a particle size of less than 50 nm are applied on the skin together with cosmetics, they can cause a problem in terms of the human body safety, and the relative surface area of the capsules containing oil-soluble ingredients can be increased, leading to a decrease in the stability of the oil-soluble active ingredients.
Thus, there is an urgent need to invent a system which can be widely used to increase the skin absorption of various oil-soluble active ingredients.